NCRI 2017: How knowing tumours inside and out is boosting progress

If you’ve noticed that the media has been abuzz with the word cancer recently, that’s not by coincidence. Scientists have been revealing their latest findings in a string of conferences all across the globe, from Lisbon’s Advanced Breast Cancer Fourth International Consensus to the International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia.

Over the past few days, Liverpool has been the source of that media excitement, housing the 13th annual National Cancer Research Institute (NCRI) Cancer Conference. The NCRI is a UK-wide partnership of various cancer research funders, including Cancer Research UK, and since coming together in 2002 these collaborators have spent a staggering £6 billion on science, said the organisation’s director Dr Karen Kennedy during her opening speech.

Without funding, research wouldn’t be possible, and the science that’s been shared throughout the NCRI conference shows the real progress that’s being made against cancer thanks to research. And this progress was reflected across the science on show, ranging from prevention to diagnosis and treatment research.

But despite this diversity, many of the presenters had something in common: they want to know tumours inside and out, from the tiny genetic changes that fuel the cancer’s growth to its complex surroundings that battle with the immune system.

So what are scientists doing to get to know cancer better?

All about that base

Cancer is rooted in DNA, so it’s unsurprising that scientists are investing a lot of effort in combing through the long strings of DNA ‘letters’ – or bases – that carry tumour cells’ genetic code. And improvements in technology are allowing scientists to gather more information from this than they ever dreamed of. Dr Jonathan McHugh from the University of Michigan in the US, said that in 2003 it cost $3,000,000,000 to crack the human genetic code for the first time. Now the same feat can be achieved for less than $1,000.

“These advances allow us to look deeper,” he said. “Defining a tumour by the organ it originated in is no longer sufficient – we need to understand the genetics of each patient’s tumour, figuring out which genes are important and trying to find the best treatment plan.”

Using a tumour’s genetic information to select the best treatment and predict how the disease might progress is one of the major ways that scientists are hoping to improve cancer care. But there are many different ways to gather such information. Dr Andrew Beggs, from the University of Birmingham and funded by Cancer Research UK, spoke of how his team is studying patterns of chemical tags found on DNA letters – called methyl groups – which can affect how a gene behaves, to help better characterise patients’ tumours. And he’s not limiting himself to cells within tumours – he’s also using patient samples to scour through the DNA of cells that have broken away and made their way into the blood.

Another pattern scientists can look for is specific changes to the letters of tumour DNA, such as ‘spelling mistakes’ where the wrong base has been added in, or it’s missing altogether. Studying these alterations can reveal what caused the cancer, as harmful substances and chemicals leave distinct patterns or ‘signatures’ that scientists can spot by studying tumour samples.

One signature that recently caused a stir was identified by speaker Dr Bin Tean Teh, from the National Cancer Centre of Singapore. He discovered that a group of molecules called aristolochic acids, which are found in several plant species commonly used in traditional Chinese medicine, are potent cancer-causing chemicals. He’s found that the distinct signatures they leave are appearing in many cancers, particularly in areas of the world where Chinese medicine is common, and is calling for a ban on the sale of such plants in medicine.

This work highlights the importance of studying these signatures, because knowing the causes of cancers could help prevent cases in the future if there are ways to limit exposure.

Causes to consequences

As well as looking at the origins of genetic changes, researchers are also studying and exploiting their consequences. Genes contain the recipes for the proteins that make up cells, and changes to the recipes can affect how these proteins look and work. As the immune system is designed to recognise things out of the ordinary, scientists are finding that the level of genetic chaos within a tumour can affect how the immune system ‘sees’ a tumour.

Using patient samples, Dr Vinod Balachandran, from the Parker Institute in the US, has found that some alterations to proteins caused by genetic changes in pancreatic cancer are better at alerting the immune system than others. Assessing the ‘quality’ of these molecules, he said, could help guide the development of new immunotherapies to better equip the immune system to attack the cancer.

While other presenters on pancreatic cancer discussed different opportunities and challenges for this disease, they all shared a sense of urgency.

“Around 90% of patients will die within a year, and the average survival is just 6 months,” said Professor Andrew Biankin, a Cancer Research UK-funded pancreatic cancer expert from the University of Glasgow. “These are things I’d like to see change.”

Balachandran and others are also studying the immune cells within and around patients’ tumours to try and find out why some can attack cancer cells while others fail. Through his work at the University of Southampton, Professor Gareth Thomas has found one obstacle to an effective attack: cancer-associated fibroblasts. These are healthy cells that become coerced into helping the tumour, and through his work in the lab Thomas has discovered that these cells can form a protective barrier that blocks immune cells.

Clearing hurdles

The diversity of research presented at NCRI serves as a reminder that there is no single solution to cancer, and that to make progress in beating the disease we need to attack it from all angles – and in smarter ways. That’s why collaboration is so important to make progress, a point that echoed throughout this year’s conference.

But as always, the research showcased gives plenty of room for hope, as well as inspiration to keep up the hard work. And the more heads that continue to come together, the more pieces of this complex puzzle will begin to slot into place, bringing solutions closer every day.

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